In recent years, with the advancement of medical research and technology, significant progress has been made in the field of blood diseases such as myelofibrosis. In this series of breakthroughs, molotinib momelotinib (omjjara) as an oral JAK1 JAK2 and ACVR1 inhibitor has recently received market authorization from the European Commission. The authorization marks the first drug approved by the European Commission for use in adult patients, including those with disease-related splenomegaly or moderate to severe anemia, covering primary myelofibrosis, post-hematoma myelofibrosis, and post-native thrombocythemia myelofibrosis, who have never received or have received ruxolitinib (rituxan) prior to the use of a JAK inhibitor.
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The market authorization for molotinib momelotinib is based on data from a subset of patients with anemia in the Phase 3 MOMENTUM trial (NCT04173494) and the Simplify-1 trial (NCT01969838). Notably, as of September 2023, the FDA has approved molotinib momelotinib for adult patients with intermediate- or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis, and patients with anemia, based on data from the same clinical studies.
The challenges of living with myelofibrosis can be heavy, and symptomatic patients may experience symptoms such as an enlarged spleen, fatigue, night sweats, and bone pain," said Nina Mojas, senior vice president of global oncology product strategy at GSK, in a press release. "Until now, there has been no drug option specifically for these patients with symptoms of anemia at the same time. The authorization of molotinib momelotinib brings a new ** option with a differentiated mechanism to these patients in the EU. ”
In Europe, about 1 in 10,000 people have myelofibrosis. It is estimated that 40% of patients have moderate to severe anaemia at the time of diagnosis, highlighting the need for additional support**, including blood transfusions. In this case, the market licensing of molotinib momelotinib offers new hope for this patient group.
In the double-blind, active-controlled MOMENTUM trial, researchers included 195 adult patients with primary myelofibrosis, post-hematopolyma myelofibrosis, or post-native thrombocythemia myelofibrosis who had received JAK inhibitors** for at least 90 days. Patients with anemia, splenomegaly, and ECOG performance status 0 to 2 were randomly assigned to receive either once-daily 200 mg of molotinib momelotinib (n = 130) or twice-daily 300 mg danazol** for 24 weeks (n = 65). The primary endpoint of the study was the Myelofibrosis Symptom Assessment Form (MFSAF v4.) at week 24 compared to baseline0) 50% or greater reduction in total symptom score (TSS). The results showed that 25% of patients in the molotinib momelotinib group had a presence in MFSAF v4A reduction of 50% or more was achieved on 0 TSS compared to only 9% in the danazol group, with a difference of 16% (95% CI, 6%-26%, p < 0.).01）。In addition, 30% of patients who received molotinib momelotinib** achieved transfusion independence compared to 20% in the danazol group, indicating a non-inferiority** difference of 14% (95% CI, 2%-25%, p = 0.).023）。Notably, 39 percent of patients in the molotinib momelotinib group achieved a spleen volume reduction response (SVR) of at least 25 percent compared with only 6 percent in the danazol group, reflecting a difference of 33 percent (95% CI, 23-44 percent, P < 0.).0001）。
In the Simplify-1 trial, researchers treated patients with myelofibrosis who had not received a JAK inhibitor (n = 432), and eligible patients received either 200 mg of molotinib once-daily or twice-daily adjusted doses of ruxolitinib** for 24 weeks. In the group of patients with hemoglobin scores below 10 g DL (n = 181), % and 24% had primary myelofibrosis, post-hematopolymatous myelofibrosis, and post-autologous thrombocythemia, respectively. Notably, the rate of transfusion independence was higher in the ruxolitinib group than in the molotinib and momelotinib group, at 44% and 29%, respectively. The primary efficacy endpoint was a 35% or greater reduction in SVR; 31.4%（95% ci，21.8%-42.3%) patients who received molotinib momelotinib** (n = 86) achieved the desired reduction in SVR, compared to 32 in the danazol group (n = 95).6%（95% ci，23.4%-43.0%）。
In MOMENTUM, the most common adverse events in patients included thrombocytopenia (all grades, 28%), diarrhea (22%), bleeding (22%), fatigue (21%), and nausea (16%). In the Simplify-1 trial, the most common adverse reactions were dizziness (24%), fatigue (22%), bacterial infection (21%), bleeding (21%), and thrombocytopenia (21%). Although 19% of patients in the optimized dose group stopped due to adverse events**, the authors stated that the overall tolerability of molotinib momelotinib in the optimized dose group suggests that this strategy may enable patients to perform it on an outpatient basis**.
Francesca Palandri, Ph.D. in Medical Oncology, University Hospital of Bologna, Italy, said: "The EU authorization of molotinib momelotinib is a meaningful step forward for eligible patients with myelofibrosis, especially for those with moderate to severe anemia who need new** options to reduce the burden associated with the disease. A single** targeting key symptoms of myelofibrosis is a clear improvement for eligible patients. ”
The European market authorization of molotinib momelotinib provides a new option for myelofibrosis** in adult patients, especially for patients with moderate to severe anemia. Behind this decision is a wealth of clinical research data showing that molotinib momelotinib has achieved significant results in reducing symptoms, improving anemia and alleviating splenomegaly. However, with the individual differences in the patient population and the diversity of needs, further monitoring and research are needed to ensure the long-term efficacy and safety of molotinib momelotinib. On the road of continuous medical advancement, we look forward to more first-class solutions to bring hope to patients.